ACOT7 p.Val128=
c.384G>A · rs553874430 · VCV3048989
Benign
No assertion criteria
Classification
Benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 1.89%, sas)
Conditions
1
ACOT7-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.57 | donor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.64 | GERP -4.9, phastCons 0.002 |
| Overall | ||
| CADD | 15.86 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.89%
South Asian · 1,724/91,080 alleles
Filtering AF
1.82%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.79%
Overall
0.113%
1,821/1,613,738 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 1.89% | 53 |
| Remaining individualsnot grpmax-eligible | 0.134% | 744 |
| Middle Eastern | 0.0502% | 1,993 |
| African / African-American | 0.00266% | 37,529 |
| East Asian | 0.00223% | 44,884 |
| European (non-Finnish) | 0.000593% | 168,578 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- ACOT7
- Protein
- p.Val128=
- Coding
- c.384G>A
- MANE Select
- NM_007274
- dbSNP
- rs553874430
- Type
- single nucleotide variant
- Location
- chr1:6339467 (GRCh38)
- Gene constraint
- LOEUF 0.468 · pLI 0.99 (gnomAD)
- Structure
- AlphaFold pLDDT 85.06 · 1 PDB
- Residue 128
- the hotdog acot-type 1 domain
Disease context
ACOT7-related disorder
Similar variants
- ACOT7 c.143+7755T>C Likely benign same condition
- ACOT7 c.144-10787G>A Likely benign same condition
- ACOT7 c.144-8956C>T Benign same condition
- ACOT7 p.Phe102= Likely benign same condition
- ACOT7 p.Thr341= Benign same condition
- ACOT7 p.Asp266= Benign ★★ same type
- ACOT7 c.143+7600C>T Uncertain significance ★ ⚠ same type
- ACOT7 c.143+7603G>T Uncertain significance ★ ⚠ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/acot7-p-val128 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown